Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China.
J Cell Mol Med. 2021 Apr;25(8):3754-3764. doi: 10.1111/jcmm.16211. Epub 2021 Feb 24.
In this study, we aimed to investigate the role of circORC2 in modulating miR-19a and its downstream signalling during the pathogenesis of STC. In this study, three groups of patients, that is healthy control (HC) group, normal transit constipation (NTC) group (N = 42) and slow transit constipation (STC) group, were, respectively, recruited. RT-PCR and Western blot analysis were exploited to investigate the changes in the expression levels of miR-19a and circORC2 in these patients, so as to establish a circORC2/miR-19a signalling pathway. The basic information of the patients showed no significant differences among different patient groups. Compared with the HC group, concentrations of neurotensin (NST) and motilin (MLN) were both significantly reduced in the NTC and STC groups, especially in the STC group. Also, miR-19a level was highest, whereas circORC2 level was lowest in the STC group. Furthermore, circORC2 was validated to sponge the expression of miR-19a, and the transfection of circORC2 reduced the expression of miR-19a. Meanwhile, MLN and NST mRNAs were both targeted by miR-19a, and the transfection of circORC2 dramatically up-regulated the expression of MLN and NST. On the contrary, the transfection of circORC2 siRNA into SMCs and VSMCs exhibited the opposite effect of circORC2. Collectively, the results of this study established a regulatory relationship among circORC2, miR-19a and neurotensin/motilin, which indicated that the overexpression of circORC2 could up-regulate the levels of neurotensin and motilin, thus exerting a beneficial effect during the treatment of STC.
在这项研究中，我们旨在研究 circORC2 在调节 miR-19a 及其在 STC 发病机制中的下游信号传导中的作用。在这项研究中，分别招募了三组患者，即健康对照组（HC）组、正常传输性便秘（NTC）组（N=42）和慢传输性便秘（STC）组。利用 RT-PCR 和 Western blot 分析来研究这些患者中 miR-19a 和 circORC2 的表达水平变化，从而建立 circORC2/miR-19a 信号通路。患者的基本信息在不同患者组之间没有明显差异。与 HC 组相比，NTC 和 STC 组的神经降压素（NST）和胃动素（MLN）浓度均明显降低，尤其是在 STC 组中。此外，miR-19a 水平在 STC 组中最高，而 circORC2 水平在 STC 组中最低。此外，circORC2 被证实可以吸附 miR-19a 的表达，并且 circORC2 的转染降低了 miR-19a 的表达。同时，miR-19a 靶向 MLN 和 NST mRNA，并且 circORC2 的转染显著上调了 MLN 和 NST 的表达。相反，circORC2 siRNA 转染到 SMCs 和 VSMCs 中表现出与 circORC2 相反的作用。总之，这项研究的结果建立了 circORC2、miR-19a 和神经降压素/胃动素之间的调节关系，表明 circORC2 的过表达可以上调神经降压素和胃动素的水平，从而对 STC 的治疗发挥有益作用。
